Congenital dyserythropoietic anemia type 1

Other Names: CDA I; Dyserythropoietic anemia, congenital type 1; Anemia, dyserythropoietic, congenital type 1; Type I congenital dyserythropoietic anemia

Congenital dyserythropoietic anemia (CDA) type 1 is an inherited blood disorder characterized by moderate to severe anemia. It is usually diagnosed in childhood or adolescence, although in some cases, the condition can be detected before birth. This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis).

Cause

CDA type I usually results from mutations in the CDAN1 gene. Little is known about the function of this gene, and it is unclear how mutations cause the characteristic features of CDA type I. Some people with this condition do not have identified mutations in the CDAN1 gene, leading researchers to believe that mutations in at least one other gene can also cause this form of the disorder.

Inheritance

Autosomal recessive inheritance, a 25% chance

CDA types I is inherited in an autosomal recessive pattern, which means both copies of the associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Symptoms

Signs and symptoms of congenital dyserythropoietic anemia type 1 (CDA1) commonly become apparent in the newborn period. Symptoms may include:

• Anemia: Which is moderate in most cases
• Jaundice
• Iron overload (hemochromatosis): Increased iron absorption may result in heart problems such as congestive heart failure and altered heart rhythm (arrhythmia), as well as liver disease (cirrhosis) and diabetes.
• Splenomegaly and/or hepatomegaly: May be absent in infants or young children, but develop later with age.
• Gallstones: May be present in some affected people.
• Skeletal findings: Specifically in the fingers and toes.
• Eye problems resulting in poor vision
• Some cases begin in childhood or adulthood, and rarely, in the fetal period, where it presents as hydrops fetalis. Other signs and symptoms that have been reported in people with CDA1 include scoliosis and vertebral defects.

Diagnosis

Congenital dyserythropoietic anemia type I (CDA I) should be suspected in individuals with the following findings:

• Moderate-to-severe macrocytic anemia with MCV >90 fL
• Inappropriately low number of reticulocytes for the degree of anemia compared to other hemolytic anemias (secondary to ineffective erythropoiesis)
• On peripheral blood smear: macrocytosis, elliptocytes, basophilic stippling, and occasional mature nucleated erythrocytes
• In bone marrow aspirate:

On light microscopy: erythroid hyperplasia, few double-nucleated erythroblasts, and interchromatin bridges between erythroblasts (in 0.6%-2.8% of erythroblasts)

On electron microscopy: erythroid precursors with spongy appearance of heterochromatin (in ≤60% of erythroblasts) and invaginations of the nuclear membrane

Other:

• Jaundice
• Splenomegaly resulting from marrow expansion secondary to ineffective erythropoiesis
• Anemia and distal limb dimorphism including hypoplastic nails and syndactyly

Treatment

Treatment consists of frequent blood transfusions and chelation therapy. Potential cures include bone marrow transplantation and gene therapy.

Prognosis

The long-term outlook (prognosis) for people with congenital dyserythropoietic anemia type 1 (CDA1) is usually good, even if life expectancy is slightly reduced in some cases. Iron overload complications can be fatal if untreated.Yearly iron overload check ups are recommended. Free iron that precipitates in the body's organs can lead to congestive heart failure, arrhythmias, diabetes, and chronic liver disease (cirrhosis).

NIH genetic and rare disease info

• NIH info on Congenital dyserythropoietic anemia type 1

Congenital dyserythropoietic anemia type 1 is a rare disease.